Acute and chronic electrical signal therapy for obesity

ABSTRACT

Apparatus is provided for treating a condition such as obesity. The apparatus includes a set of one or more electrodes, which are adapted to be applied to one or more respective sites in a vicinity of a body of a stomach of a patient. A control unit is adapted to drive the electrode set to apply to the body of the stomach a signal, configured such that application thereof increases a level of contraction of muscle tissue of the body of the stomach, and decreases a cross sectional area of a portion of the body of the stomach for a substantially continuous period greater than about 3 seconds.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of co-pending U.S. patent applicationSer. No. 10/795,803, filed May 28, 2003, which in turn is a continuationof U.S. patent application Ser. No. 09/734,358, filed Dec. 11, 2000, nowissued as U.S. Pat. No. 6,600,953, all of which are incorporated hereinby reference.

FIELD OF THE INVENTION

The present invention relates generally to treatment of obesity, andspecifically to invasive techniques and apparatus for treating obesity.

BACKGROUND OF THE INVENTION

Invasive treatments for obesity are often recommended for patients witha body mass index (mass/height2 [kg/m2]) which is greater than 35 or 40.For such patients, their weight is commonly associated with increasedrisk of heart disease, diabetes, and arthritis. Preferably, the invasivetreatments are accompanied by changes in lifestyle, such as improvedeating habits and an appropriate exercise regimen.

U.S. Pat. No. 6,067,991 to Forsell, U.S. Pat. No. 5,601,604 to Vincent,and U.S. Pat. No. 5,234,454 to Bangs, and U.S. Pat. Nos. 5,449,368,5,226,429 and 5,074,868 to Kuzmak, which are incorporated herein byreference, describe mechanical instruments for implantation in or aroundthe stomach of an obese patient.

U.S. Pat. No. 5,690,691 to Chen et al., which is incorporated herein byreference, describes a gastric pacemaker for treating obesity and otherconditions. The pacemaker includes multiple electrodes which are placedat various positions on the gastrointestinal (GI) tract, and whichdeliver phased electrical stimulation to pace peristaltic movement ofmaterial through the GI tract.

U.S. Pat. No. 5,423,872 to Cigaina, which is incorporated herein byreference, describes apparatus for applying electrical pulses to thedistal gastric antrum of a patient, so as to reduce the motility of thestomach and to thereby treat obesity or another condition.

U.S. Pat. Nos. 5,188,104 and 5,263,480 to Wernicke et al., which areincorporated herein by reference, describe a method for stimulating thevagus nerve of a patient so as to alleviate an eating disorder.

U.S. Pat. Nos. 6,104,955, 6,091,992, and 5,836,994 to Bourgeois, U.S.Pat. No. 6,026,326 to Bardy, and U.S. Pat. No. 3,411,507 to Wingrove,which are incorporated herein by reference, describe the application ofelectrical signals to the GI tract to treat various physiologicaldisorders.

PCT Patent Publication WO 99/03533 to Ben Haim et al., entitled, “Smoothmuscle controller,” and U.S. patent application Ser. No. 09/481,253 inthe national phase thereof, both of which are assigned to the assigneeof the present patent application and are incorporated herein byreference, describe apparatus and methods for applying signals to smoothmuscle so as to modify the behavior thereof. In particular, apparatusfor controlling the stomach is described in which a controller appliesan electrical field to electrodes on the stomach wall so as to modifythe reaction of muscle tissue therein to an activation signal, while notgenerating a propagating action potential in the tissue. In the contextof the present patent application and in the claims, the use of such anon excitatory signal to modify the response of one or more cells toelectrical activation thereof, without inducing action potentials in thecells, is referred to as Excitable Tissue Control (ETC). Use of an ETCsignal is described with respect to treating obesity, by applying theETC signal to the stomach so as to delay or prevent emptying of thestomach. In addition, a method is, described for increasing the motilityof the gastrointestinal tract, by applying an ETC signal to a portion ofthe tract in order to increase the contraction force generated in theportion.

PCT Patent Publication WO 97/25098, to Ben Haim et al., entitled“Electrical muscle controller,” and the corresponding U.S. patentapplication Ser. No. 09/101,723, which are assigned to the assignee ofthe present patent application and are incorporated herein by reference,describe methods for modifying the force of contraction of a heartchamber by applying an ETC signal to the heart.

SUMMARY OF THE INVENTION

It is an object of some aspects of the present invention to provideimproved apparatus and methods for treatment of medical conditions whichrelate to the gastrointestinal tract.

It is a further object of some aspects of the present invention toprovide improved apparatus and methods for treating obesity.

In preferred embodiments of the present invention, apparatus fortreating a condition such as obesity comprises a set of one or moreelectrodes which are applied to one or more sites of thegastrointestinal (GI) tract of a patient. A control unit preferablydrives the electrode set to apply an Excitable Tissue Control (ETC)signal to the GI tract, so as to modulate contraction of muscles of thegastrointestinal tract and to thereby treat the condition.

In a preferred embodiment, the electrodes are applied to the stomach,and the control unit drives the electrodes to apply an enhancementsignal which includes, as appropriate, the ETC signal and/or anexcitatory signal. Thus, the enhancement signal may induce contractionsand/or increase or otherwise modify the contraction forces generated bymuscles of the stomach.

For some applications, the enhancement signal is applied so as to modifya contraction pattern of some of the stomach's muscles, in order toreduce the cross sectional area of a portion of the stomach. The narrowring thereby generated reduces the volume of a region of the stomach,and increases the sensation of satiety felt by the patient compared tothat which would be felt without the application of this embodiment ofthe invention. For example, the enhancement signal may cause an“indenting” of the stomach wall, whereby food is limited in its abilityto vacate the esophageal region of the stomach. Consequently, thisportion of the stomach is stretched more than usual for the volume offood ingested, and an earlier sensation of satiety is induced. Thisembodiment thus employs electrical signals to cause a narrowing of thestomach analogous to that produced mechanically by the gastric bandsdescribed in the Background section of the present patent application.Unlike these prior art mechanical bands, however, this application ofthe present invention allows the extent of the narrowing to be moderatedin real time by the control unit without mechanical intermediaries(e.g., modulation of fluid pressure).

Alternatively or additionally, the enhancement signal is applied, priorto and/or during a meal, so as to reduce the overall size of thestomach, thereby increasing the tension in the wall of the stomach whenfood is in the stomach. This increased tension typically yields acorresponding increase in the patient's sensation of satiety, and thussubstantially reduces the likelihood of the patient overeating.

Further alternatively or additionally, repeated application of theenhancement signal engenders a long term shortening of muscle fibers ofthe stomach, and, consequently, a reduction of the size of the stomach,even at times when the signal is not being applied. Thus, for example,the enhancement signal may be applied, intermittently throughout theday, over a period of days, weeks, or months, so as to induce desiredstructural changes in the stomach which last, preferably, for at leastseveral days or weeks after removal of the signal. Advantageously, dueto the stomach's reduced size, it is typically stretched during andafter a meal to a greater extent than would occur without application ofthe enhancement signal, and thus greater sensations of satiety are feltby the patient. Optionally, the signal may be applied when the patient'sstomach is expected to be relatively empty (e.g., each morning for onehour prior to the patient waking up), so as to maximize the extent towhich the muscle fibers are able to shorten in response to the signal.

For some patients, it is desirable to apply the enhancement signalaccording to a schedule, whereby constriction of the stomach induces afeeling of satiety at times when the patient might choose to eat butshould not be eating. At other times, e.g., when the patient issleeping, the signal is typically not applied. Alternatively oradditionally, the enhancement signal is (a) applied during one or moremeals during the day, so as to reduce the patient's appetite duringthose meals, and (b) removed during meals eaten during the remainder ofthe day, so as to prevent nutritional deficiencies which might occur insome patients from any inappropriate, excessive use of the signalsdescribed herein.

In a preferred embodiment, the enhancement signal is applied to musclein one portion of the stomach, so as to induce and/or modify acontraction of the stimulated muscle which, in turn, causes stretchingof stretch receptors in an adjacent portion of the stomach. This form ofcontraction mediated stretching simulates the normal satiety signalingof the stomach's stretch receptors, without the patient having eaten thequantities of food which would normally be required to trigger thissatiety response.

Alternatively or additionally, some or all of the electrodes are placedin a vicinity of the pyloric sphincter, and the control unit drives theelectrode set to apply the enhancement signal so as to increase acontraction force of the sphincter. The increased force typicallyreduces the sphincter's cross section, and thereby generally extends aperiod of time in which partially digested food remains in the stomach.

In a preferred embodiment, one or more electrodes are applied to or in avicinity of respective sites of the arterial supply of the patient'ssmall intestine. Typically, the control unit drives some or all of theelectrodes to apply signals which cause a controllable level ofconstriction of the arteries to which these electrodes are coupled. Theconstriction produced thereby preferably transiently and controllablyreduces the blood flow to the small intestine, and, it is believed,thereby reduces the total number of calories which are ultimatelyabsorbed into the patient's bloodstream during and after eating a meal.

There is therefore provided, in accordance with a preferred embodimentof the present invention, apparatus for treating a condition, including:

a set of one or more electrodes, adapted to be applied to one or morerespective sites in a vicinity of a stomach of a patient; and

a control unit, adapted to drive the electrode set to apply an ExcitableTissue Control (ETC) signal to the sites, configured such thatapplication thereof decreases a cross sectional area of at least aportion of the stomach.

Preferably, the set of one or more electrodes includes a first set ofone or more electrodes, and the apparatus includes a second set of oneor more electrodes, adapted to be applied to one or more respectivesites in a vicinity of a pyloric sphincter of the stomach. The controlunit is preferably adapted to drive the second electrode set to apply anETC signal configured such that application thereof increases acontraction force of the sphincter and extends a period of time in whichpartially digested food remains in the stomach.

Further preferably, the control unit is adapted to configure the ETCsignal such that application thereof decreases the cross sectional areaof the portion of the stomach by at least 20%, for a substantiallycontinuous period greater than about one minute.

Still further preferably, the portion of the stomach includes a firstportion of the stomach, and the control unit is adapted to configure theETC signal such that ingestion of food by the patient in conjunctionwith application of the ETC signal to the first portion inducesstretching of a stretch receptor in a second portion of the stomach thatinduces a sensation of satiety.

In a preferred embodiment, the control unit is adapted to drive theelectrode set to apply the signal over a sufficient time period so as toengender a long term structural change of the stomach.

Typically, the electrode set is adapted to be applied in contact withmuscle tissue of the stomach.

The control unit is preferably adapted to configure the ETC signal suchthat the decreased cross sectional area impedes passage of ingestathrough the stomach.

Alternatively or additionally, the control unit is adapted to configurethe ETC signal such that application thereof decreases a volume of thestomach.

In some preferred embodiments of the present invention, the control unitis adapted to configure a timing parameter of the ETC signal responsiveto timing of natural gastric electrical activity. The ETC signal istypically applied as a series of biphasic pulses. Preferably, thecontrol unit is adapted to configure the ETC signal to have a durationof at least about 1 second. Further preferably, the duration is at leastabout 3 seconds.

For some applications, the apparatus includes at least one stimulatingelectrode, and the control unit is adapted to drive the stimulatingelectrode to apply an excitatory signal to muscle tissue of the stomachin conjunction with driving the electrode set to apply the ETC signal.In these cases, the control unit is typically adapted to drive thestimulating electrode to apply gastric pacing pulses to the stomach.

Preferably, the control unit is adapted to receive a patient signal,input by the patient, and to drive and withhold driving the electrodeset responsive to the patient signal.

The control unit is typically adapted to drive the electrode set inaccordance with a schedule programmed into the control unit. Forexample, the control unit may be adapted to drive the electrode setduring at least one meal eaten by the patient during a 24 hour period,and to withhold driving the electrode set during another meal eaten bythe patient during the 24 hour period. Alternatively or additionally,the control unit is adapted to withhold driving the electrode set duringtime periods designated as times when the patient generally does noteat.

For some applications, the control unit is adapted to drive at least oneof the electrodes to apply an excitatory pulse in conjunction with theETC signal. Preferably, the control unit is adapted to drive the atleast one electrode to apply the excitatory pulse as a biphasic pulse.Alternatively or additionally, the control unit is adapted to drive theat least one electrode to initiate applying the ETC signal at leastabout 100 ms following a termination of the excitatory pulse.Preferably, the control unit is adapted to drive the at least oneelectrode to initiate applying the ETC signal less than about 1000 msfollowing a termination of the excitatory pulse.

Preferably, the control unit is adapted to drive the electrode set whilethe patient is eating. The control unit may, for example, be adapted toreceive a patient signal, input by the patient, indicative of thepatient eating. In this case, the control unit is preferably adapted toreceive by way of the patient signal an indication of a nutritionalquality of food being eaten by the patient and to configure a parameterof the ETC signal responsive to the patient signal.

Alternatively or additionally, the apparatus includes a sensor which isadapted to convey to the control unit a signal responsive to the patienteating. As appropriate, the sensor may include a blood sugar sensor or amechanical sensor. Alternatively or additionally, the sensor includes asensing electrode, adapted to be coupled in a vicinity of agastrointestinal tract of the patient. For some applications, thesensing electrode includes one of the one or more electrodes.

Preferably, the sensor is adapted to convey the signal responsive to aquantity of food ingested by the patient, and the control unit isadapted to withhold driving the electrode set, as appropriate,responsive to the quantity (e.g., if the quantity is less than athreshold quantity).

In a preferred embodiment, the control unit is adapted to configure theETC signal such that application thereof decreases the cross sectionalarea of a region of the stomach, and maintains the decreased crosssectional area in the region for a duration greater than about 10seconds.

In a preferred embodiment, the control unit is adapted to configure theETC signal such that application thereof increases intra gastricpressure, thereby inducing a sensation of satiety.

For some applications, the apparatus includes a second set of one ormore electrodes, adapted to be applied to one or more respective sitesin a vicinity of the lower esophageal sphincter. The control unit ispreferably adapted to drive the second electrode set to apply a signalto the sphincter, configured such that application thereof increases acontraction force generated by the sphincter.

There is further provided, in accordance with a preferred embodiment ofthe present invention, apparatus for treating a condition, including:

a set of one or more electrodes, adapted to be applied to one or morerespective sites in a vicinity of a pyloric sphincter of a stomach of apatient; and

a control unit, adapted to drive the electrode set to apply an ExcitableTissue Control (ETC) signal to the sites, configured such thatapplication thereof increases a contraction force of the sphincter andextends a period of time in which partially digested food remains in thestomach.

Preferably, the control unit is adapted to configure the ETC signal suchthat driving the electrode set to apply the ETC signal increases thecontraction force for a substantially continuous period greater thanabout one minute.

As appropriate, the electrode set may be adapted to be applied incontact with muscle tissue of an antral portion of the stomach and/or incontact with muscle tissue of the sphincter.

There is still further provided, in accordance with a preferredembodiment of the present invention, apparatus for treating a condition,including:

a set of one or more electrodes, adapted to be applied to one or morerespective sites in a vicinity of a body of a stomach of a patient; and

a control unit, adapted to drive the electrode set to apply to the bodyof the stomach a signal configured such that application thereofincreases a level of contraction of muscle tissue of the body of thestomach, and decreases a cross sectional area of a portion of the bodyof the stomach for a substantially continuous period greater than about3 seconds.

Preferably, the control unit is adapted to configure the signal suchthat application thereof decreases the cross sectional area of theportion for a substantially continuous period greater than about 10seconds.

There is yet further provided, in accordance with a preferred embodimentof the present invention, apparatus for treating a condition, including:

a set of one or more electrodes, adapted to be applied to one or morerespective sites in a vicinity of a first portion of a stomach of apatient; and

a control unit, adapted to drive the electrode set to apply to theportion of the stomach a signal configured such that application thereofincreases a level of contraction of muscle tissue of the portion, andconfigured such that ingestion of food by the patient in conjunctionwith application of the signal induces stretching of a stretch receptorin a second portion of the stomach.

Preferably, the control unit is adapted to drive the electrode set toapply the signal to a body of the stomach, and to configure a parameterof the signal such that the increased level of contraction of the muscletissue impedes passage of ingesta through the stomach and increases alevel of tension in a fundic wall of the stomach.

There is also provided, in accordance with a preferred embodiment of thepresent invention, apparatus for treating a condition, including:

a set of one or more electrodes, adapted to be applied to one or morerespective sites on an arterial supply of small intestine of a patient;and

a control unit, adapted to drive the electrode set to apply a signal tothe sites, configured such that application thereof induces constrictionof one or more arteries in the arterial supply and decreases a quantityof digestion products which are absorbed into blood of the patient fromthe small intestine.

Preferably, the control unit is adapted to determine an approximate timeof initiation of eating, and to initiate driving the electrode set toapply the signal at least ten minutes subsequent thereto. Typically, thecontrol unit is adapted to determine the approximate time of initiationof eating responsive to receiving a patient signal, input by thepatient.

In a preferred embodiment, the apparatus includes a sensor which isadapted to convey to the control unit a signal indicative of food beingin a gastrointestinal tract of the patient.

There is additionally provided, in accordance with a preferredembodiment of the present invention, apparatus for treating a condition,including:

a set of one or more electrodes, adapted to be applied to one or morerespective sites of a stomach of a patient; and

a control unit, adapted to drive the electrode set to apply to thestomach, over a sufficient time period, a sequence of pulses configuredso as to engender a long term structural change of the stomach.

Preferably, the control unit is adapted to configure the sequence ofpulses as an Excitatory Tissue Control (ETC) signal. Alternatively oradditionally, the control unit is adapted to configure a parameter ofthe sequence of pulses such that the application of the pulses over thetime period is such as to engender a continuation of the structuralchange for at least two days following a termination of the applicationof the pulses.

Preferably, the control unit is adapted to configure a parameter of thesequence of pulses such that the application of the pulses over the timeperiod is such as to reduce a characteristic length of muscle fibers ofthe stomach. Alternatively or additionally, the control unit is adaptedto configure a parameter of the sequence of pulses such that theapplication of the pulses over the time period is such as to reduce acharacteristic size of the stomach.

For some applications, the control unit is adapted to drive theelectrode set to apply the pulses for at least two days. Preferably, thecontrol unit is adapted to drive the electrode set to apply the pulsesfor at least two weeks.

In a preferred embodiment, the control unit is adapted to drive theelectrode set in accordance with a schedule programmed into the controlunit. For example, the control unit may be adapted to drive theelectrode set at times when the patient's stomach is generally empty, orduring a meal eaten by the patient.

There is yet additionally provided, in accordance with a preferredembodiment of the present invention, a method for treating a condition,including:

applying an Excitable Tissue Control (ETC) signal to one or more sitesin a vicinity of a stomach of a patient; and

configuring the ETC signal such that application thereof to the one ormore sites decreases a cross sectional area of at least a portion of thestomach.

There is still additionally provided, in accordance with a preferredembodiment of the present invention, a method for treating a condition,including:

applying an Excitable Tissue Control (ETC) signal to one or more sitesin a vicinity of a pyloric sphincter of a stomach of a patient; and

configuring the ETC signal such that application thereof to the one ormore sites increases a contraction force of the sphincter and extends aperiod of time in which partially digested food remains in the stomach.

There is also provided, in accordance with a preferred embodiment of thepresent invention, a method for treating a condition, including:

applying a signal to one or more sites in a vicinity of a body of astomach of a patient; and

configuring the signal such that application thereof to the one or moresites increases a level of contraction of muscle tissue of a portion ofthe body of the stomach, and decreases a cross sectional area of theportion for a substantially continuous period greater than about 3seconds.

There is further provided, in accordance with a preferred embodiment ofthe present invention, a method for treating a condition, including:

applying a signal to one or more sites in a vicinity of a first portionof a stomach of a patient; and

configuring the signal such that the application thereof increases alevel of contraction of muscle tissue of the portion and stretches astretch receptor in a second portion of the stomach.

There is still further provided, in accordance with a preferredembodiment of the present invention, a method for treating a condition,including:

applying a signal to one or more sites on an arterial supply of smallintestine of a patient; and

configuring the signal such that application thereof to the sitesinduces constriction of one or more arteries in the arterial supply anddecreases a quantity of digestion products which are absorbed into bloodof the patient from the small intestine.

There is yet further provided, in accordance with a preferred embodimentof the present invention, a method for treating a condition, including:

applying a sequence of pulses over a time period to one or more sites ofa stomach of a patient; and

configuring the sequence of pulses such that application thereof to theone or more sites engenders a long term structural change of thestomach.

The present invention will be more fully understood from the followingdetailed description of the preferred embodiments thereof, takentogether with the drawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a schematic illustration of a stomach, showing the placementof electrodes and sensors thereon, in accordance with a preferredembodiment of the present invention;

FIG. 1B is a schematic illustration of the stomach of FIG. 1A, in acontracted state thereof responsive to the application of an electricalsignal thereto, in accordance with a preferred embodiment of the presentinvention;

FIG. 2 is a schematic block diagram of a control unit, which generatessignals to be applied to the electrodes shown in FIG. 1A, in accordancewith a preferred embodiment of the present invention;

FIG. 3A is a graph showing an electrical signal applied to the stomachof a dog, in accordance with a preferred embodiment of the presentinvention, and deformations of the stomach produced in response to theapplied signal;

FIGS. 3B and 3C are graphs illustrating details of the electrical signalshown in FIG. 3A, in accordance with respective preferred embodiments ofthe present invention; and

FIG. 4 is a schematic illustration of the vasculature supplying asection of small intestine, showing the placement of electrodes andsensors thereon, in accordance with a preferred embodiment of thepresent invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Reference is now made to FIGS. 1A and 1B. FIG. 1A is a schematicillustration of gastric control apparatus 18, which applies electricalenergy to modify the activity of a portion of the gastrointestinal tractof a patient, in accordance with a preferred embodiment of the presentinvention. Apparatus 18 typically comprises an implantable or externalcontrol unit 90, which drives one or more electrodes 100 to apply anenhancement signal to respective sites on or in a vicinity of thepatient's stomach 20 and/or elsewhere on or in a vicinity of sites onthe gastrointestinal tract. At least some of the sites are preferablylocated on the body of the stomach, i.e., that portion of the stomachlocated between the lower esophageal sphincter and the pyloricsphincter. The enhancement signal is preferably configured so as tomodulate contraction of muscles of the stomach and to thereby treat acondition such as obesity. FIG. 1B is a schematic illustration ofstomach 20 in a contracted state thereof, responsive to the applicationof the enhancement signal thereto in accordance with a preferredembodiment of the present invention.

Preferably, the enhancement signal includes, as appropriate, anExcitable Tissue Control (ETC) signal and/or an excitatory signal whichinduces contraction of muscles of the stomach. Aspects of ETC signalapplication are typically performed in accordance with techniquesdescribed in the above referenced PCT Publications WO 99/03533 and WO97/25098 and their corresponding US national phase applications Ser.Nos. 09/481,253 and 09/101,723, mutatis mutandis. For some applications,the ETC signal is applied responsive to natural electrical activity ofstomach 20, for example, after a designated delay following a detectedactivation of a portion of the stomach. For these applications, it ispreferable to use apparatus and methods described in Israel PatentApplication 129,257, entitled “Trigger based regulation of excitabletissue control in the heart,” mutatis mutandis. This application isassigned to the assignee of the present invention and is incorporatedherein by reference. Alternatively, the ETC signal is applied subsequentto an artificial gastric pacing pulse, as described hereinbelow.

Typically, control unit 90 drives electrodes 100 to apply theenhancement signal so as to create a contraction pattern of some of themuscles of stomach 20, such as the contraction shown in FIG. 1B, inorder to reduce the cross sectional area of a portion 22 of the stomach.This reduction is believed to increase the sensation of satiety felt bythe patient compared to that which was felt prior to application of theenhancement signal. Typically, the enhancement signal is configured suchthat the cross sectional area of the stomach is reduced by at least 20%,and this reduction is maintained in one region of the stomach for aperiod of at least one minute. It is to be understood that for someapplications, greater or lesser reductions in cross sectional area maybe desirable, and these may be maintained for periods greater or lessthan one minute.

Electrodes 100 preferably comprise one or more signal applicationelectrodes 30, which may also operate in a sensing mode. In addition,one or more dedicated local sense electrodes 74 are preferably placed onor in stomach 20, and convey electrical signals to control unit 90responsive to natural gastric electric activity. Further preferably, oneor more mechanical sensors 70 (e.g., accelerometers, force transducers,strain gauges, or pressure gauges) are coupled to the control unit andare placed on or in the stomach. Alternatively or additionally, one ormore supplemental sensors 72 (e.g., pH sensors, blood sugar sensors,intragastric pressure sensors and/or sonometric sensors) are coupled tothe control unit and are placed on or in the gastrointestinal tract orelsewhere on or in the patient's body. The control unit preferablymodifies the waveform applied through electrodes 100 responsive tosignals from sensors 70 and 72 and local sense electrodes 74, asdescribed hereinbelow with reference to FIG. 2. Typically, control unit90 and the above mentioned electrodes and sensors are permanently orsemi permanently implanted in or coupled to the patient's body. (Forclarity, connections between control unit 90 and only some of theelectrodes and sensors are shown in FIG. 1A.)

Electrodes 100 are typically coupled to the serosal layer of the stomachand/or inserted into the muscular layer of the stomach. Alternatively oradditionally, the electrodes are coupled elsewhere on the stomach,gastrointestinal tract, or to other suitable locations in or on thepatient's body. The number of electrodes and sensors, as well as thepositions thereof, are shown in FIG. 1A by way of example, and othersites on stomach 20 or in a vicinity thereof are appropriate forelectrode and sensor placement in other applications of the presentinvention. Different types of electrodes known in the art are typicallyselected based on the specific manifestation of the patient's condition,and may comprise stitch, coil, screw, patch, basket, needle and/or wireelectrodes, or substantially any other electrode known in the art ofelectrical stimulation or sensing ih tissue.

Preferably, control unit 90, electrodes 100, and the various sensorsdescribed herein are implanted in the patient in a manner generallysimilar to that used to implant gastric pacemakers or other apparatusfor stimulating the gastrointestinal tract which are known in the art.As appropriate, techniques described in one or more of the patents citedin the Background section of the present patent application may beadapted for use with these embodiments of the present invention.

FIG. 2 is a schematic block diagram of control unit 90, in accordancewith a preferred embodiment of the present invention. Mechanical sensors70, supplemental sensors 72, local sense electrodes 74, and electrodes100 are preferably coupled to provide feedback signals to a digestiveactivity analysis block 80 of control unit 90. The feedback signalsgenerally provide block 80 with information about various aspects of thestomach's present state (e.g., empty or full) and the stomach's level ofactivity, so as to enable block 80 to analyze the signals and actuatecontrol unit 90 to modify the electrical energy applied to electrodes100 responsive to the analysis. Preferably, the enhancement signal isadjusted by the control unit responsive to the feedback signals in orderto yield a desired response, e.g., an indication by mechanical sensors70 of a desired level of muscle contraction within portion 22, or anindication by supplemental sensors 72 of maintenance of the patient'sblood sugar level within a desired range. Advantageously, the ability toturn the enhancement signal on or off at any time, in order to modulatethe stomach's shape, provides a generally safer and more effectivealternative to prior art, purely mechanical techniques for remodelingthe stomach.

For some applications, control unit 90 drives electrodes 100 to applythe enhancement signal according to a schedule, so as to induceconstriction of stomach 20 at times when the patient should not beeating, or when the patient's eating should be minimized. Alternativelyor additionally, the enhancement signal is (a) applied during one ormore meals during the day, so as to reduce the patient's appetite duringthose meals, and (b) removed during the remainder of the day, so as toprevent counterproductive remodeling of the stomach.

Alternatively or additionally, the patient activates, deactivates, andmodulates the level of signal application in accordance with physician'sinstructions, aspects of the patient's diet, or other factors. Forexample, the patient may eat soup and salad at dinner, and then activatethe control unit using operator controls 71, so as to increase the senseof satiety prior to being presented with a large selection of highcalorie options for an entree. The patient may subsequently input acommand for a higher level of signal application during dessert, suchthat the patient will feel very full, and, in fact, not have space forthe dessert. It is seen through this example that this embodiment of thepresent invention can be used to encourage the patient to fully satisfyall nutritional needs, while simultaneously reducing or eliminating thehunger sensation which the patient would otherwise feel if stomach 20were not in the contracted state induced by the enhancement signal.

For some applications, control unit 90 drives electrodes 100 to applythe enhancement signal to muscle in one area of stomach 20, so as toinduce a contraction of the stimulated muscle which, in turn, causesstretching of stretch receptors in an adjacent portion of the stomach.This form of contraction mediated stretching simulates the normalappetite reduction action of the stomach's stretch receptors, withoutthe patient having eaten the quantities of food which would normally berequired to trigger this appetite reduction response. For example, thecontrol unit may generate an enhancement signal which causes contractionof the corpus of the stomach at the beginning of a meal, whereby asubstantial amount of food will accumulate in the fundus. Thisaccumulation, in turn, increases intra gastric pressure and stretchesthe fundic walls to a greater extent than would be caused without theapplied enhancement signal. If it is determined that a patient hasintermittent in response to the increased intra gastric pressure, thenit is preferable to additionally apply the enhancement signal to thelower esophageal sphincter, so as to increase the contraction forcethereof and reduce or eliminate the reflux.

Alternatively or additionally, some or all of electrodes 100 are placedin a vicinity of the pyloric sphincter 24 of stomach 20, and controlunit 90 drives these electrodes to apply the ETC signal so as toincrease a contraction force of the sphincter. Although it is known inthe art to apply pacing or other excitatory signals to the sphincterwith the intention of contracting the sphincter and increasing the timein which food remains in the stomach, the inventors believe that theseprior art methods do not effectively achieve a sufficient level ofconstriction of the sphincter, and therefore do not engender the optimumweight loss of the patient. By contrast, application of the ETC signalto muscle in the gastrointestinal tract has been shown (see gastroesophagealreflux episodes FIG. 3) to substantially increase contractionforce above that obtained by pacing alone.

As shown in FIG. 2, digestive activity analysis block 80 typicallyconveys results of its analysis of the inputs from mechanical sensors70, supplemental sensors 72, and electrodes 100 to a “parameter searchand tuning” block 84 of control unit 90, which iteratively modifiescharacteristics of the electrical energy applied to stomach 20 in orderto attain a desired response. Preferably, operating parameters of block84 are entered, using operator controls 71, by a physician or otherhuman operator of the control unit. Block 84 typically utilizesmultivariate optimization and control methods known in the art in orderto cause one or more of the aforementioned mechanical, electrical,chemical and/or other measured parameters to converge to desired values.

In general, each one of electrodes 100 may convey a particular waveformto stomach 20, differing in certain aspects from the waveforms appliedby the other electrodes. The particular waveform to be applied by eachelectrode is determined by control unit 90, preferably under the initialcontrol of the operator. Aspects of the waveforms which are set by thecontrol unit, and may differ from electrode to electrode, typicallyinclude parameters such as time shifts between application of waveformsat different electrodes, waveform shapes, amplitudes, DC offsets,durations, and duty cycles. For example, although the waveforms appliedto some or all of electrodes 100 usually comprise a train of biphasicsquare waves following a natural or applied pacing pulse, otherwaveforms, such as a sinusoid, one or more monophasic square waves, or awaveform including an exponentially varying characteristic, could beapplied to other electrodes. Generally, the shape, magnitude, and timingof the waveforms are optimized for each patient, using suitableoptimization algorithms as are known in the art.

Preferably, desired signal parameters are conveyed by block 84 to asignal generation block 86 of control unit 90, which generates,responsive to the parameters, electrical signals that are applied byelectrodes 100 to the stomach. Block 86 preferably comprises amplifiers,isolation units, and other standard circuitry known in the art ofelectrical signal generation.

In an initial calibration procedure, parameter search and tuning block84 preferably modifies a characteristic (e.g., timing, magnitude, orshape) of the enhancement signal applied through one of electrodes 100,and then determines whether a predetermined response generally improvesfollowing the modification. For example, one or more of mechanicalsensors 70 may be used to determine the extent to which the shape ofstomach 20 changes responsive to corresponding changes in the appliedenhancement signal. In a series of similar calibration steps, block 84repeatedly modifies characteristics of the energy applied through eachof the electrodes, such that those modifications that improve theresponse are generally maintained, and modifications that cause it toworsen are typically eliminated or avoided. Preferably, the calibrationprocedure is subsequently performed by the physician at intermittentfollow up visits, and/or by unit 90 automatically during regular use ofapparatus 18 (e.g., daily).

In a preferred embodiment, the calibration procedure additionallycomprises determining a schedule for the application of the enhancementsignal at various sites on the stomach. For example, it may bedetermined for some patients that it is advantageous to: (a) apply theenhancement signal to the sites in a wave, which simulates the naturalflow of electrical activity in the stomach, (b) maintain the shapemodification for a specified period (e.g., 5 15 minutes), (c) remove thesignal for a relaxation period (e.g., 1 5 minutes), and (d) return tostep (a).

Preferably, during the initial calibration procedure, the locations ofone or more of electrodes 100 are varied while the enhancement signal isapplied therethrough, so as to determine optimum placement of theelectrodes. In a series of calibration steps, each electrode is movedover an area of stomach 20, and an appropriate response of the stomachis measured. After the physician considers that a sufficient number ofsites have been investigated to characterize the area, the electrode isreturned to the site yielding the best response. Subsequently, otherelectrodes, placed on, in, or near the stomach are moved according tothe same protocol, so as to achieve substantially optimum placement ofsome or all of the electrodes.

Based on results of the calibration procedure and/or an analysis ofother factors pertaining to the patient's condition, the physiciantypically determines whether the ETC signal should be applied subsequentto an artificial pacing pulse or in response to natural electricalactivity of the stomach. In the former case, the ETC signal ispreferably applied in a vicinity of a site where standard gastric pacingpulses are applied. Further preferably, the ETC signal is appliedthrough the same electrode as that through which a gastric pacing pulseis applied.

Alternatively, stomach 20 generates the gastric rhythm, substantiallywithout artificial pacing. In such modes, local sense electrodes 74 and,optionally, some or all of electrodes 100, convey electrical signals tocontrol unit 90, so as to enable parameter search and tuning block 84 tosynchronize the electrical signals applied by electrodes 100 with thenatural electrical activity of the stomach. It will be understood thatalthough electrodes 74 and 100 are shown for clarity of explanation asseparate entities, a single set of electrodes may be used to performboth functions.

FIG. 3A is a graph showing an electrical signal applied to the stomachof a dog, in accordance with a preferred embodiment of the presentinvention, and deformations of the stomach produced in response to theapplied signal. In this experiment, two stitch electrodes were insertedapproximately 3 centimeters apart through the serosa of the antral areaof the stomach, into the muscularis. Throughout the experiment, theelectrodes applied 20 mA peak to peak biphasic pacing pulses, each phaselasting for 300 milliseconds. Successive pacing pulses were separated by20 seconds. In addition, during two periods, ETC signals havingcharacteristics described hereinbelow with reference to FIGS. 3B and 3Cwere applied following the pacing pulses. The deformation of the outerwall of the stomach responsive to the applied signals was measuredcontinuously by a strain gauge placed on the stomach between theelectrodes.

FIGS. 3B and 3C are graphs showing details of the applied pacing pulsesand ETC signals shown in FIG. 3A, in accordance with respectivepreferred embodiments of the present invention. During the periodlabeled in FIG. 3A, “Pacing & ETC I,” an ETC signal lasting 1000milliseconds was applied starting 500 milliseconds after each pacingpulse. The ETC signal itself comprised a series of biphasic squarecurrent pulses (+10 mA, 10 mA), each phase having a 50 millisecondduration. During the period labeled in FIG. 3A, “Pacing & ETC II,” anETC signal having the same parameters was applied to the stomach, exceptthat the duration of the “ETC II” signal application was 4000milliseconds.

With reference to FIG. 3A, during an approximately two minute warm upperiod, small deformations are seen to be produced by each of the pacingpulses. These deformations are believed to generally correspond to thelevels of deformation produced due to natural gastric electricalactivity. Following this pacing only warm up period, the “Pacing & ETCI” signal described hereinabove was applied for about two minutes,during which increased contraction strength by the dog's stomachproduced increased deformations, which are clearly visible in FIG. 3A.Subsequently, the “ETC I” signal was removed, and a pacing only periodwas recommenced, resulting in a complete return to baseline (pre ETC)contraction levels. Lastly, during the “Pacing & ETC II” perioddescribed hereinabove, deformation of the stomach increasedsignificantly above baseline, and remained significantly above baselinevalues for the approximately two minute duration of the signalapplication. For clinical applications, similar signals are preferablyapplied through a larger number of electrodes in order to attain andmaintain the constriction of the stomach depicted in FIG. 1B.

FIG. 4 is a schematic illustration depicting apparatus 118 for treatingobesity or another condition of a patient, in accordance with apreferred embodiment of the present invention. Apparatus 118 preferablycomprises a control unit 190, and one or more electrodes 200 applied toor in a vicinity of respective sites of the arterial supply 130 of thepatient's small intestine 120. If appropriate, some or all of electrodes200 may be placed on the superior mesenteric artery 110, or in avicinity thereof. Typically, control unit 190 drives electrodes 200 toapply signals which cause a controllable level of constriction of thearteries to which these electrodes are coupled. Alternatively oradditionally, other transducers (not shown) are implanted in the patientin a vicinity of arterial supply 130, and are driven by control unit 190to induce some or all of the arteries in supply 130 to contract. Asappropriate, these transducers may induce this contraction usingmechanical or chemical means. The constriction produced by apparatus 118preferably transiently and controllably reduces the blood flow to smallintestine 120, and thereby reduces the total number of calories whichare ultimately absorbed into the patient's bloodstream during and aftereating a meal.

For some applications, it is advantageous to utilize apparatus 118 inconjunction with apparatus 18, in order to reduce the patient's weightin a quicker manner than would likely be realized when using eitherapparatus alone. Alternatively, apparatus 118 may be used withoutsimultaneous use of apparatus 18, for example, if it is determined thatthe patient is likely to try and “cheat” apparatus 18 by drinking highcalorie liquid foods, whose digestion might not be affected by apparatus18 to the same extent as that of solid foods. For instance, it is knownthat many patients who have mechanical gastric restriction bands drinkhigh calorie milk shakes in order to evade mechanical bands.

Preferably, apparatus and methods described hereinabove with respect toapparatus 18 are utilized, mutatis mutandis, in the operation ofapparatus 118. Thus, for example, control unit 190 may drive electrodes200 to apply an ETC signal and/or pulses and/or other signal forms tomodulate arterial supply 130. Additionally, control unit 190 preferablyvaries parameters of the applied electrical energy responsive tofeedback from mechanical sensors 70 and/or supplemental sensors 172,which are typically applied to small intestine 120, in a vicinitythereof, or elsewhere on or in the patient's body.

Preferably, but not necessarily, the electrical energy is applied attimes which are likely to produce maximum weight loss, without adverselyaffecting the patient's nutritional intake, and without significantlyreducing the patient's comfort. Thus, for example, one of supplementalsensors 172 may comprise a blood sugar monitor, which inhibits controlunit 190 from applying the electrical energy when the patient's bloodsugar is below a determined threshold. Alternatively or additionally,operation of apparatus 118 is initiated or supplemented responsive to aparameter of the contents of small intestine 120, such as an indicationby sensors 172 of the lipid concentration thereof. Further alternativelyor additionally, the patient is enabled to activate apparatus 118 (e.g.,during and after eating dessert, or for a determined time period whenthe patient is going to sleep) and to deactivate the apparatus (e.g.,when the patient has a headache, or has orally taken a medication).Still further alternatively or additionally, apparatus 118 is activateda fixed or variable time (e.g., 10 30 minutes) following initiation of ameal, when it is expected that some digestive products will have reachedthe small intestine.

Preferably, a calibration period is provided for apparatus 118, whichprovides some or all of the calibration options described hereinabovewith respect to apparatus 18. In addition, safe signal applicationdurations and activation sequences of electrodes 200 are preferablydetermined during the calibration period, such that small intestine 120continually has a sufficient level of blood flowing therethrough tosupport normal activity of the tissue of the small intestine.

For some applications, an intestinal enhancement signal is applied toelectrodes 174 coupled to respective sites on small intestine 120.Preferably, control unit 190 drives electrodes 174 to apply theintestinal enhancement signal so as to increase the contraction forcegenerated by muscle of small intestine 120. This increased contractionforce, in turn, decreases the period of time in which digestion productsremain in the intestine, and, therefore, decreases the quantity of thesedigestion products which are ultimately absorbed into the patient'sbloodstream. As appropriate, the intestinal enhancement signal maycomprise an ETC component and/or other signals known in the art forstimulating tissue. Moreover, the intestinal enhancement signal may beapplied in combination with, or separately from, the signals applied toelectrodes 100 and/or 200, described hereinabove.

It will be appreciated by persons skilled in the art that the presentinvention is not limited too what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1. Apparatus for treating a condition, comprising: a set of one or moreelectrodes, adapted to be applied to one or more respective sites in avicinity of a stomach of a patient; and a control unit, adapted to drivethe electrode set to apply an Excitable Tissue Control (ETC) signal tothe sites, configured such that application thereof decreases a crosssectional area of at least a portion of the stomach.